BSR and BHPR guideline for the treatment of systemic sclerosis

Abstract

SSc is a complex, multi-organ disease that requires a comprehensive multidisciplinary guideline. This is a short summary of the guideline, which is available in full as supplementary material at Rheumatology Online. Each recommendation is graded for level of evidence (I-IV) and strength (A-D). Patients are classified as having SSc based on current classification criteria (ACR/EULAR 2013 [1]). Other scleroderma spectrum diseases are not included in this document. Figure 1 summarizes a general approach to management of SSc. Overview of management of SSc The principles of current management of SSc are summarized. Once a confirmed diagnosis is established, all patients can be designated as either lcSSc or dcSSc subset based upon the extent of skin thickening. Proximal skin involvement, involving skin of trunk or proximal limbs, is designated diffuse. Cases with overlap disease should be identified so that overlap features may be treated concurrently with SSc. All patients require symptomatic treatment, and both limited and diffuse cases should be treated for vascular manifestations. Active, early dcSSc requires immunosuppressive treatment. In all cases of SSc, vigilant follow-up to determine significant organ-based complications is mandatory. dcSSc: diffuse cutaneous SSc; lcSSc: limited cutaneous SSc; GI: gastrointestinal. Management of early diffuse cutaneous SSc (dcSSc) should occur within the framework of a multidisciplinary team. Early recognition and diagnosis of dcSSc is a priority, with referral to a specialist SSc centre (III, C). Patients with early dcSSc should be offered an immunosuppressive agent: MTX, MMF or i.v. CYC (III/C), although the evidence base is weak. Some patients might later be candidates for autologous haemopoietic stem cell transplant (ASCT; see below). D-Pen is not recommended (IIa/C). ASCT may be considered in some cases, particularly where there is risk of severe organ involvement, balancing concerns about treatment toxicity (IIa/C). Skin involvement may be treated with either MTX (II, B) or MMF (III, C). Other options include CYC (III, C), oral steroid therapy (in as low a dose as possible to suppress symptoms, and with close monitoring of renal function; III, C) and possibly rituximab (III, C). AZA or MMF should be considered after CYC to maintain improvement in skin sclerosis and/or lung function (III, C). RP is almost universal and can be treated by vasodilators, but benefit must be balanced against side-effects. Around half of patients with SSc report a history of digital ulceration that reflects more structural vasculopathy. Severe digital ulcers (DUs) are those causing or threatening tissue destruction or when three or more occur in 1 year. These should be considered for advanced therapy, such as sildenafil, iloprost or bosentan [2]. First-line treatments are calcium channel blockers (Ia, A) and angiotensin II receptor antagonists (Ib, C). Other treatments that may be considered are: selective serotonin reuptake inhibitors, α-blockers and statin therapy (III, C). Phosphodiesterase type 5 inhibitors are being used increasingly for SSc-related RP (IIa, C). Intravenous prostanoid (e.g. iloprost; Ia, B) and digital (palmar) sympathectomy (with or without botulinum toxin injection) should be considered in severe and/or refractory cases (III, D). DUs require integrated management by a multidisciplinary team; management includes local and systemic treatment (III, C). Oral vasodilator treatment should be optimized, analgesia optimized and any infection promptly treated (III, C). Sildenafil should now be used before considering i.v. prostanoids and bosentan, in line with the current National Health Service (NHS) England Clinical Commissioning policy [3] (I, A). In severe active digital ulceration, patients should receive i.v. prostanoid (Ia, B). In patients with recurrent, refractory DUs, a phosphodiesterase type 5 inhibitor (IIa, B) or i.v. prostanoid (Ia, B) and an endothelin receptor antagonist (including bosentan; Ia, B) should be considered. Digital (palmar) sympathectomy (with or without botulinum toxin injection) may also be considered in severe and/or refractory cases (III, D). Up to 80% of SSc patients will develop interstitial lung disease, but this may be mild and stable. Immunosuppression should be considered when extensive or progressive disease is confirmed. All SSc cases should be evaluated for lung fibrosis. Treatment is determined by the extent and severity and the likelihood of progression to severe disease (I, A). CYC by i.v. infusion is recommended (I, A/B), and MMF may also be used as an alternative or after CYC (II, B). For patients living in England, treatments are initiated through a designated Pulmonary Hypertension Centre (see NHS England A11/S/a) according to the national commissioning policy for treatment of pulmonary arterial hypertension (PAH; NHS England/A11/P/b and NHS Commissioning Board (NHSCB)/A11/P/a), reflecting expert recommendations [4]. Diagnos